Education:

Research Summary:

Matsui’s group is working in the fields of Nanotechnology and Biotechnology and
the integration of these two areas (i.e., Bionanotechnology) is producing
creative sciences with high technology impacts. Matsui’s research interests
consist of; 1. 3D Assembly of Nanomaterials using peptide framework (target: solar cells, metamaterials, electronics, optics), 2. Reconfigurable/programable self-assembly system, 3. Development of cancer cell sensing silicon chips 4. Origin of life discovering catalytic peptides (i.e., enzyme-mimic) through virus evolution.

The ability to control self-assembly of complex 2D
and 3D architectures from functional building blocks could allow further
development of complex device configurations. By mimicking natural systems,
genetically engineered peptides with a variety of functional building blocks such
as metal NPs can be applied to design new materials with the specificity of
assembled structure, the robustness of assembly, and the versatility of the
superstructure. Here, we present three types of large-scale (µm3 ~ mm3) biomimetic 2D and 3D assemblies
using nanoscale collagen peptides as building blocks. The first example is to
mimic bone tissues for the production of free-standing flexible collagen films.
In this case, biotylated collagen peptides are assembled into films with
streptavidin-functionalized QDs, which are used as molecular recognition-based
cross-linking agents between biomolecular film domains to provide structural
reinforcement and flexibility. The second example is to mimic S-layer proteins
on bacteria and we assemble microcapsules from collagen peptides stable even in
extreme pH or high temperature when the peptides are assembled on oil-in water
droplets and the ends of peptides are capped/cross-linked by peptide-binding
proteins. The third example is to assemble 3D reconfigurable superstructure
crystals from collagen peptides in the large-scale with high yield. In this
strategy, biotylated collagen peptides and ligand-functionalized nanoparticle
hubs are self-assembled into 3D microcrystals in controlled structures and NP
density with the precise nanoscale interparticle distance. This simple, rapid
fabrication protocol produces
high yields of 3D materials in controlled shapes, promising ease and flexibility in
manufacturing future functional devices.
The reconfigurability of the 3D directed assembly was also demonstrated
by modifying peptides with genetic engineering. We discovered that the
conformation change of peptide building blocks induced by pH could trigger the
disassembly of the hybrid NP-peptide cube and undergo the reassembly into
different shapes. One of innovative applications for reconfigurable assembly is to develop autonomous metal-organic-framework (MOF) motors driven by re-assembly of peptides from inside to outside of MOF.

Another part of Matsui'research is to develop biosensor chips for detecting cancer cells. One of
the best strategies to halt cancer’s progress is the development of new
diagnostic tools that allow one to detect the disease in an early stage. It
would be desirable to develop simple and robust cancer detection systems
without using unreliable biomarkers for a variety of tumor grades regardless of
its origin in early stages. The development of non-invasive screening device
for cancers with high specificity and selectivity enables more frequent
monitoring of the early stage disease development, progress, recovery, and
recurrence of cancers. Here we developed a new cancer detection platform
incorporating electric cancer cell sensors on silicon chips. This sensing
platform was designed to distinguish cells in different sizes and shapes by
measuring their characteristic impedance signals on polysilicon
microelectrodes. Due to the softness of cancer cells as compared to normal
cells, cancer cells were observed to swell three times more than normal cells
under hyposmotic pressure. By using this sensor chip and protocol, cancer cells can be distinguished from normal cells
electronically without biomarkers; as strong hyposmotic stress is applied
to cells, only cancer cells increase impedance
signals due to the distinguished mechanical property. For example, we have
examined six different cancer cell lines from prostate, kidney, ovarian, and
breast, and all of these cancer cells were observed to expand their size about
35 – 50 % under osmotic pressure and their swellings could be detected
sensitively and selectively by the robust impedance measurements of the sensor
chip on the order of 10 cells/mL in less than 30 minutes even in
contaminated samples. Recently, we improved the
protocol to detect cancer cells in urine samples. Finally, the
aggressive breast cancer cells could be distinguished from less aggressive ones
by measuring impedance values of the samples, opening the possibility that
circulating tumor cells (CTC), cancer stem cell (CSC), or metastatic cancer
cells may be detected by this technique.

The third part is for the discovery of new catalytic peptides through virus evolution. The
amide bond is fundamental to life. It acts as the strong chemical linkage
between amino acids as they combine to form proteins. As such, its high
stability against spontaneous hydrolysis at physiological conditions is
paramount, with an estimated half-life of 600 years for internal peptide bonds. Nonetheless, several key processes in the
biological world involve the breaking (hydrolysis) and reforming (condensation)
of the amide bond. Through evolution, nature has generated a variety of
amidolytic catalysts in the form of enzymes that enable both effective
hydrolysis and condensation of amide bonds. Despite a series of impressive
advances in the last 30 years, most notably using catalytic antibodies, our ability to mimic this behavior through the de novo design and discovery of
amidolytic catalysts that operate under physiological conditions and can
hydrolyse internal peptide bonds has been unsuccessful. our
strategy of catalytic capture via
condensation-driven gelation, combined with phage display was successful in the
identification of four different dodeca peptides which specifically catalyze
the formation/cleavage of amide bonds. These peptides can spontaneously fold
into minimal catalytic triads. The
result reported here would break through the prescriptive concept that
catalytic oligopeptides cannot acquire the substrate-specificity because of the
lack of complicated 3D structures that enzymes posses. This concept is also applicable to discover catalytic peptides to grow a variety of semiconductor nanomaterials at room temperature. To demonstrate the proof-of-concept, we examined to
find catalytic peptides for room-temperature growth of ZnO nanocrystal by this
approach. The combinatory phage display library identified the small number of
peptide sequences for the ZnO growth and one of them, ZP-1 peptide,
demonstrated the strong catalytic activity for the room temperature growth.